The Response of IL-17-Producing B Cells to ArtinM Is Independent of Its Interaction with TLR2 and CD14

Oliveira-Brito, Patrícia Kellen Martins; Roque-Barreira, Maria Cristina; Silva, Thiago Aparecido da

doi:10.3390/molecules23092339

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…Anti‐IgM, IL‐4, and sCD40L stimulation resulted in a lower frequency of B10 cells in CRIF1‐deficient B cells than in WT B cells (Figure 4E). To determine the production of IL‐17 in CRIF1‐deficient B cells, splenic B cells from WT and Crif1 ΔCD19 mice were cultured with IL‐6, IL‐1β, and IL‐23 for 6 days (31). Increased IL‐17 levels were detected in the supernatants of stimulated CRIF1‐deficient B cells, whereas IL‐10 production was decreased.…”

Section: Resultsmentioning

confidence: 99%

B Cell–Specific Deletion of CR6‐Interacting Factor 1 Drives Lupus‐like Autoimmunity by Activation of Interleukin‐17, Interleukin‐6, and Pathogenic Follicular Helper T Cells in a Mouse Model

Park

Yang

Hwang

et al. 2022

Arthritis & Rheumatology

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Objective CR6‐interacting factor 1 (CRIF1) is a nuclear transcriptional regulator and a mitochondrial inner membrane protein; however, its functions in B lymphocytes have been poorly defined. This study was undertaken to investigate the effects of CRIF1 on B cell metabolic regulation, cell function, and autoimmune diseases. Methods Using mice with B cell–specific deletion of CRIF1 (Crif1ΔCD19 mice), we assessed the relevance of CRIF1 function for lupus disease parameters, including anti–double‐stranded DNA (anti‐dsDNA), cytokines, and kidney pathology. RNA sequencing was performed on B cells from Crif1ΔCD19 mice. The phenotypic and metabolic changes in immune cells were evaluated in Crif1ΔCD19 mice. Roquinsan/+ mice crossed with Crif1ΔCD19 mice were monitored to assess the functionality of CRIF1‐deficient B cells in lupus development. Results Crif1ΔCD19 mice showed an autoimmune lupus‐like phenotype, including high levels of autoantibodies to dsDNA and severe lupus nephritis with increased mesangial hypercellularity. While loss of CRIF1 in B cells showed impaired mitochondrial oxidative function, CRIF1‐deficient B cells promoted the production of interleukin‐17 (IL‐17) and IL‐6 and was more potent in helping T cells develop into follicular helper T cells. In a mouse model of autoimmune lupus, depletion of CRIF1 in B cells exacerbated lupus severity, and CRIF1 overexpression prevented lupus development in roquinsan/san mice. Conclusion These results demonstrated that CRIF1 negatively correlates with disease severity and that overexpression of CRIF1 ameliorates disease development. Our findings suggest that CRIF1 is essential for preventing lupus development by maintaining B cell self tolerance.

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Section: Resultsmentioning

confidence: 99%

B Cell–Specific Deletion of CR6‐Interacting Factor 1 Drives Lupus‐like Autoimmunity by Activation of Interleukin‐17, Interleukin‐6, and Pathogenic Follicular Helper T Cells in a Mouse Model

Park

Yang

Hwang

et al. 2022

Arthritis & Rheumatology

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“…We have determined that the interaction of ArtinM with N-glycans linked to glycoproteins on the cell surface, such as TLR2/CD14 and CD3εγ, provides the primary mechanism for triggering the production of cytokines responsible for the immunomodulation induced by ArtinM [8,22,50,51]. However, the recognition of TLR2/CD14 N-glycans does not account for the ArtinM activity that induces murine B cells to produce IL-17 and IL-12p40 [26]. Notably, the subcutaneous administration of ArtinM to naive BALB/c mice, besides affecting immune cells, increases the number of splenic B cells [52], suggesting that B cells contribute to the immunomodulatory activity of ArtinM in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Suspensions of spleen cells obtained from mice were prepared as reported by Oliveira-Brito et al [26] using the B cell enrichment kit (Pan B Cell Isolation Kit, Miltenyi Biotec, EUA), according to the manufacturer’s instructions. The negatively selected cells were stained with PE Rat Anti-Mouse CD19 (BD Pharmingen™) antibodies and analyzed by flow cytometry (Guava® easyCyte, Millipore, EUA).…”

Section: Methodsmentioning

confidence: 99%

ArtinM Cytotoxicity in B cells derived from Non-Hodgkin’s Lymphoma is regulated by CD45 phosphatase activity and Src family kinases

Barboza

Thomaz

Carvalho

et al. 2022

Preprint

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Receptors on the immune cell surface have a variety of glycans that may account for the immunomodulation induced by lectins, which have a carbohydrate recognition domain (CRD) that binds to monosaccharides or oligosaccharides in a specific manner. ArtinM, a D-mannose-binding lectin obtained from Artocarpus heterophyllus, has affinity for the N-glycans core. Immunomodulation by ArtinM toward the Th1 phenotype occurs via its interaction with TLR2-CD14 N-glycans on antigen-presenting cells, as well as recognition of CD3 gamma chain; N-glycans on murine CD4+ and CD8+ T cells. ArtinM exerts a cytotoxic effect on Jurkat human leukemic T cell line and human myeloid leukemia cell line (NB4). The current study evaluated the effects of ArtinM on murine and human B cells derived from non-Hodgkins lymphoma. We found that murine B cells are recognized by ArtinM via the CRD, and the ArtinM stimulus did not augment the proliferation rate or production of IL-2. However, murine B cells incubation with ArtinM augmented the rate of apoptosis, and this cytotoxic effect of ArtinM was also seen in human B cell lines sourced from non-Hodgkins lymphoma Raji cell line. This cytotoxic effect was inhibited by the phosphatase activity of CD45 on Lck, and the protein kinases of the Src family contribute to cell death triggered by ArtinM.

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“…Activation of murine CD4⁺ and CD8⁺ T cells by ArtinM result in increased release of IL-2 and IFN-γ [47]. Furthermore, ArtinM activates murine B cells, increasing IL-17 and IL-12p40 production [48].…”

Section: Discussionmentioning

confidence: 99%

The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation

et al. 2020

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Mast cells are connective tissue resident cells with morphological and functional characteristics that contribute to their role in allergic and inflammatory processes, host defense and maintenance of tissue homeostasis. Mast cell activation results in the release of pro-inflammatory mediators which are largely responsible for the physiological functions of mast cells. The lectin ArtinM, extracted from Artocarpus heterophyllus (jackfruit), binds to D-manose, thus inducing degranulation of mast cells. ArtinM has several immunomodulatory properties including acceleration of wound healing, and induction of cytokine release. The aim of the present study was to investigate the role of ArtinM in the activation and proliferation of mast cells. The rat mast cell line RBL-2H3 was used throughout this study. At a low concentration (0.25μg/mL), ArtinM induced mast cell activation and the release of IL-6 without stimulating the release of pre-formed or newly formed mediators. Additionally, when the cells were activated by ArtinM protein tyrosine phosphorylation was stimulated. The low concentration of ArtinM also activated the transcription factor NFkB, but not NFAT. ArtinM also affected the cell cycle and stimulated cell proliferation. Therefore, ArtinM may have therapeutic applications by modulating immune responses due to its ability to activate mast cells and promote the release of newly synthesized mediators. Additionally, ArtinM could have beneficial effects at low concentrations without degranulating mast cells and inducing allergic reactions.

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The Response of IL-17-Producing B Cells to ArtinM Is Independent of Its Interaction with TLR2 and CD14

Cited by 10 publications

References 34 publications

B Cell–Specific Deletion of CR6‐Interacting Factor 1 Drives Lupus‐like Autoimmunity by Activation of Interleukin‐17, Interleukin‐6, and Pathogenic Follicular Helper T Cells in a Mouse Model

B Cell–Specific Deletion of CR6‐Interacting Factor 1 Drives Lupus‐like Autoimmunity by Activation of Interleukin‐17, Interleukin‐6, and Pathogenic Follicular Helper T Cells in a Mouse Model

ArtinM Cytotoxicity in B cells derived from Non-Hodgkin’s Lymphoma is regulated by CD45 phosphatase activity and Src family kinases

The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation

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